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| Highlights from the Four NIGMS Funded Academic Centers of Excellence |
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Introduction: The National Institute of General Medical Sciences
(NIGMS) granted support to four academic centers in the US designated as the Centers of Excellence in Chemical Methodologies and Library Development, to invigorate the drug development pipeline and to broaden opportunities and resources for biomedical research. This session will showcase the developments that have been made in each of the four centers toward this goal. |
7:00-8:30 Coffee and Registration
8:30-8:50 The CMLD Initiative and the NIH Roadmap: Experiments in Experimental Science
Dr. John M. Schwab, Program Director, Division of Pharmacology, Physiology, and Biological Chemistry, National Institute of General Medical Sciences, National Institutes of Health
This introductory talk will present the background and motivation behind the National Institute of General Medical Sciences (NIGMS) Chemical Methodologies and Library Development (CMLD) center grant program. The relationship between the CMLD program and certain aspects of the NIH Roadmap also will be discussed, as well as insights on how these Federal initiatives are intended to complement activities within the pharmaceutical industry.
8:50-9:20 Multicomponent Synthesis of Libraries Inspired by Peptides and Alkaloids
Dr. Jeffrey Aube, Professor and Interim Chair, Department of Medicinal Chemistry,
University of Kansas
The development of new methods for the convergent assembly of sterechemically rich heterocycles will be described. Peptidomimetic libraries loosely based on turn topographies are assembled through a ring expansion of carbo- and heterocyclic ketones with hydroxyalkyl azides, which correspond to naturally occurring amino acids and analogs. In related chemistry, condensed multicyclic analogs were prepared using domino reactions that combine the azido-Schmidt reaction with methods of carbon- carbon bond formation, which include the Diels-Alder reaction.
9:20-9:50 Microwave- Assisted Synthesis of Small Molecule Libraries
Dr. Stefan Werner, Research Assistant Professor, Assistant Director, University
of Pittsburgh, Center for Chemical Methodologies & Library Development
The hydrozirconation of alkynes with zirconocene hydrochloride and the dimethylzinc-mediated addition of alkenylzirconocenes to diphenylphosphinoyl imines are greatly accelerated with microwave irradiation, resulting in a convenient and rapid one-pot process for the preparation of allylic amines. These form building blocks for a library of allyl and C-cyclopropylalkylamides, carbamates and sulfonamides. In a second library realized by the UPCMLD, microwave irradiation facilitated the synthesis of tricyclic pyrroles in a Stetter-Paal-Knorr reaction sequence.
9:50-10:20 Expanding Chemical Diversity using Stereocontrolled Synthesis
Dr. James S. Panek, Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU)
Boston University
Complex molecules often provide opportunities for the preparation of new structures ("diversity exploration") with a goal to increase the structural diversity available from nature and prepare molecules with novel chemical or biological properties. This presentation will outline examples from our research program illustrating our overall interest in expanding chemical diversity, including examples of projects being conducted at the Center for Chemical Methodology and Library Development at Boston University (CMLD-BU). Projects involving the synthesis of chemical libraries utilizing stereochemical and positional variation within the molecular framework, as well as new methodologies to enable parallel synthesis of new scaffold architecture will be described.
10:20-10:50 Coffee Break
10:50-11:20 Concise, Stereoselective Approaches to Libraries of Structurally Diverse
Small Molecules
Dr. Jared Shaw, Institute Fellow, ICCB, Harvard Medical School
Two approaches to the split/pool synthesis of skeletally diverse small molecule libraries have been developed with the goal of uncovering new probes for biological processes. Our approach to synthesizing compounds with broad core-structure diversity relies on the selective introduction of proximal functional groups which react to determine the final three-dimensional structure.
11:20-11:30 Enabling Tools to Probe Biology: Chemistry Considerations
Dr. Christopher Lipinski, Adjunct Senior Research Fellow, Exploratory Medicinal Sciences, Pfizer Inc.
One extreme, the chemistry in the tool itself is 'drug-like',
although the tool does not have all the necessary attributes required of a drug. The other extreme, the chemistry in the tool is not drug-like; chemistry 'flaws' are present that mean the compound could not be used to treat human disease but the tool is selective enough to probe biology. Chemistry false positives and negatives are minimized if HTS is considered as a process rather than a screen. This is more of a challenge in academia than in industry.
11:30-12:00 Panel: Translating Novel Chemistry from Academic Groups to Drug Development
Dr. Christopher A. Lipinski, Adjunct Senior Research Fellow, Pfizer Inc.
Dr. John M. Schwab, Program Director, National Institutes of Health
Dr. Daryl R. Sauer, Group Leader, High-Throughput Organic Synthesis, Abbott
Laboratories
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12:15-1:00 Luncheon Technology Workshop
Recent Advances in Microwave Assisted Organic Synthesis
Dr. Farah Mavandadi, Scientific Support and Education Manager
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Sponsored by
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| As precise control of reaction conditions encourages medicinal chemists to include microwave technology as a standard tool in organic chemistry laboratories, technological advances in microwave-assisted organic synthesis
(MAOS) continue to grow. Combining productivity enhancing tools such as microwave synthesis and high-performance flash chromatography significantly speed up the drug development process. This talk will address the recent advances in combining the MAOS with other cutting edge techniques for rapid production of organic compound libraries.
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Microwave Synthesis
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Introduction:
Simultaneous Cooling/Irradiation - The Microwave Effect is a novel approach using microwave synthesis that is gaining respect in the community. The opening talk will give details followed by a discussion of microwave enabled
chemistries.
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1:20-1:30 Chairperson's Remarks
Dr. C. Oliver Kappe, Institute of Chemistry, Karl-Franzens-University Graz
1:30-2:00 Is there Magic in Microwave-Promoted Synthesis?
Dr. Nicholas Leadbeater, Assistant Professor, Chemistry, University of Connecticut
The existence or not of non-thermal microwave effects will be discussed. There have been a number of reports discussing why microwave heating leads to such rapid product formation and in some cases non-thermal effects have been suggested. We have performed a series of experiments to probe the existence of non-thermal effects in a range of chemical reactions and will present our findings here.
2:00-2:30 Enabling Chemistries and Microwaves
Dr. Christopher Hulme, Head, High-Throughput Medicinal Chemistry, Eli Lilly & Co.
This talk will detail several one-pot procedures, facilitated by microwave irradiation, allowing the rapid introduction of molecular complexity. A novel one pot oxidation using microwave driven hypervalent iodine chemistry will also be revealed.
2:30-3:00 Refreshment Break
3:00-3:30 New Applications of Microwave-Assisted Organic Synthesis in Drug Discovery
and Materials Science
Dr. Scott E. Wolkenberg, Technology Enabled Synthesis Group, Merck and Co., Inc.
The continuing acceptance and now widespread use of microwave synthesizers has enabled the rapid discovery of new reactions, the development of significant improvements to established thermal conditions, and the application of these in areas as diverse as drug discovery and materials science. Recent results from our laboratory in these areas will be described including a novel strategy for the generation of diverse heterocycles from common intermediates and preliminary work towards the preparation of functional ionic liquids.
3:30-4:00 Microwave-Assisted Synthesis - A
Maturing Science
Dr. C. Oliver Kappe, Institute of Chemistry, Karl-Franzens-University Graz
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4:00-5:30 Technical Microwave Synthesizer End-Users Group Meeting and Cocktails |
Featuring
Five Top Technical
Tips from a Panel
of Experts |
• Interested in purchasing a microwave synthesizer?
Attend this session to consider your options
• New to the microwave synthesis field? - Get technical tips from established users
• Established User? - Contribute to discussion and take home some new ideas
Featuring Top Five Technical Tips from a Panel of Experts
This session will feature a series of short presentations from end-users of all three microwave instruments, followed by an in-depth Q&A and one-on-one round table sessions with the audience. A summary of questions and answers raised at each round table will be included in the follow-up conference proceedings emailed directly to you.
Dr. C. Oliver Kappe, Institute of Chemistry, Karl-Franzens-University Graz
Dr. Daryl R. Sauer, Group Leader, High-Throughput Organic Synthesis, Abbott Laboratories
Dr. Christopher Hulme, Head, High-Throughput Medicinal Chemistry, Lilly Corporate Center, Eli Lilly and Company
Dr. Nicholas Leadbeater, Assistant Professor, Chemistry, University of Connecticut
Dr. Stefan Werner, Assistant Director, University of Pittsburgh, Center for Chemical Methodologies & Library Development
Dr. Scott E. Wolkenberg, Technology Enabled Synthesis Group, Merck and Co., Inc.
Dr. Valey Fokin, Associate Professor, The Scripps Research Institute
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5:30-6:30 An Evening with Chris Lipinski
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Ever wondered where the "rule of 5" began?
Join Chris Lipinski for a reflection on the career
of a lifetime!
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